Placental cell treatment for critical limb ischemia patient subpopulations

Abstract

Disclosed herein are methods and compositions comprising placental adherent stromal cells for treating peripheral ischemic disease, for example critical limb ischemia in specific patient subpopulations; and methods of selecting subjects having peripheral ischemic disease, for example critical limb ischemia, amenable for treatment with placental adherent stromal cells.

1 . (canceled) 
     
     
         2 . A method for treating critical limb ischemia (CLI) or increasing amputation-free survival (AFS) in a subpopulation of CLI subjects, comprising selecting a CLI subject wherein the subject has a normal glycemic status; and administering a therapeutically effective amount of a population of placental adherent stromal cells (ASC), therefore treating CLI or increasing amputation-free survival (AFS). 
     
     
         3 . A method of treating critical limb ischemia (CLI) in a patient, the method comprising the steps of:
 (a) determining whether the patient has diabetes mellitus; and   (b) if the patient does not have diabetes mellitus, then intramuscularly administering placental ASC to the patient, and   (c) if the patient does have diabetes mellitus, then administering an alternative therapy to the patient.   
     
     
         4 . The method of  claim 3  wherein said step of determining whether the patient has diabetes mellitus is performed by:
 (i) obtaining or having obtained a biological sample(s) from the patient; and 
 (ii) performing or having performed an assay on the biological sample to measure a parameter selected from the group consisting of hemoglobin AIC glycosylation, post-prandial plasma glucose level, and fasting plasma glucose level. 
 
     
     
         5 . The method of  claim 4  wherein said treating CLI comprises one or more of increasing AFS, decreasing likelihood of requiring revascularization, decreasing likelihood of developing gangrene, inhibiting development of necrosis, healing wounds, decreasing likelihood of worsening of wounds, or improving perfusion of an ischemic limb. 
     
     
         6 . A method of increasing amputation-free survival (AFS) in a subject with critical limb ischemia (CLI), comprising:
 a. screening the subject for the presence or absence of diabetes mellitus;   b. administering placental adherent stromal cells (ASC) to the subject if said diabetes mellitus is determined to be absent; and   c. applying an alternative therapy to the subject if said diabetes mellitus is determined to be present, thereby increasing AFS in a subject with CLI.   
     
     
         7 . (canceled) 
     
     
         8 . A composition for treating critical limb ischemia (CLI), comprising placental adherent stromal cells (ASC), wherein said composition is indicated for use in a subject with normal glycemic status. 
     
     
         9 . The composition of  claim 8  wherein said treating CLI comprises one or more of increasing AFS, decreasing likelihood of requiring revascularization, decreasing likelihood of developing gangrene, inhibiting development of necrosis, healing wounds, decreasing likelihood of worsening of wounds, or improving perfusion of an ischemic limb. 
     
     
         10 . A composition for increasing amputation-free survival (AFS) in a subject with critical limb ischemia (CLI), comprising placental adherent stromal cells (ASC), wherein said composition is indicated for use in a subject with normal glycemic status. 
     
     
         11 . The composition of  claim 8 , where said composition is an injected composition. 
     
     
         12 . The composition of  claim 8 , wherein said placental ASC have been incubated on a 2D substrate. 
     
     
         13 . The composition of  claim 8 , wherein said placental ASC have been incubated on a 3D substrate. 
     
     
         14 . (canceled) 
     
     
         15 . The composition of  claim 13 , wherein said 3D culture substrate comprises a synthetic adherent material. 
     
     
         16 . (canceled) 
     
     
         17 . The composition of  claim 15 , wherein said synthetic adherent material is selected from the group consisting of a fibrous matrix, a polyester, a polypropylene, a polyalkylene, a polyfluorochloroethylene, a polyvinyl chloride, a polystyrene, and a polysulfone. 
     
     
         18 . The composition of  claim 13 , wherein said 3D culture apparatus comprises microcarriers disposed within a bioreactor. 
     
     
         19 . The composition of  claim 8 , wherein said placental ASC are allogeneic to said subject. 
     
     
         20 . The composition of  claim 8 , wherein the composition is intramuscularly injected. 
     
     
         21 . The composition of  claim 8 , comprising 100-600 million of said placental ASC, for an adult subject. 
     
     
         22 . The composition of  claim 8 , wherein said placental ASC express a marker selected from the group consisting of CD73, CD90, CD29 and CD105. 
     
     
         23 . The composition of  claim 8 , wherein said placental ASC do not express a marker selected from the group consisting of CD3, CD4, CD11b, CD14, CD19, and CD34. 
     
     
         24 . (canceled) 
     
     
         25 . The composition of  claim 8 , wherein said placental ASC do not express a marker selected from the group consisting of CD3, CD4, CD34, CD39, and CD106. 
     
     
         26 . (canceled) 
     
     
         27 . (canceled)